Stress and hippocampal volume in rodents, a longitudinal study

压力对记忆的影响至少部分是由于它对海马体的影响，海马体是大脑中对学习和记忆至关重要的区域。虽然慢性应激可以减少海马体体积，但海马体萎缩的功能意义尚不清楚。很难理解海马体萎缩的功能意义，部分原因可能是几乎完全使用横断面方法来研究应激和非应激个体之间的海马体体积差异。然而，横断面研究未能揭示因果关系。另一个问题与大多数压力研究中未能控制个体压力易感性的差异有关。对经历过大规模创伤事件的人进行的精神病理学调查显示，并不是所有的人都同样受到这些事件的影响，因此一些人对创伤具有弹性。*这一新的NSERC应用程序是建立在我的实验室的一个新兴的长期目标之上的，目的是揭示应激诱导的海马区萎缩的功能意义和机制。使用非侵入性核磁共振方法测量压力暴露前后的海马体体积，我们发现对慢性社会失败应激敏感的小鼠表现出应激诱导的体积变化。尽管如此，这些变化并没有在对长期社会失败有弹性的小鼠身上发现。我们的短期目标是使用这个社会失败模型，它允许我们将对慢性应激敏感或有弹性的小鼠分离出来，以检验以下假设：1)有弹性的小鼠表现出对应激诱导的海马区收缩的抵抗；2)慢性应激对背侧和腹侧海马区的体积产生相反的影响，这两个区分别负责空间记忆和情绪记忆的形成；3)应激诱导的海马区萎缩与树突重组和小胶质细胞的增殖有关。本研究的结果不仅可以加深我们对应激诱导的海马区萎缩的功能意义和机制的理解，而且可以为纵向研究小鼠脑结构的变化开辟一条新的研究途径。这项研究计划是对我的实验室正在进行的研究的补充，该研究旨在调查应激对海马区突触功能的影响。这个研究项目的培训可以让受训者在老鼠身上使用非侵入性成像方法，这是一种强大但新兴的研究技术，可以帮助他们在学术界和工业界发展自己的职业生涯。

The impact of stress on memory is at least partly due to its influences on the hippocampus, a brain region that is important for learning and memory. Although chronic stress could reduce hippocampal volume, the functional significance of hippocampal shrinkage remains unclear. The difficulty of understanding the functional significance of hippocampal shrinkage may be partly caused by the almost exclusive use of a cross-sectional approach to investigate hippocampal volume differences between stressed and non-stressed individuals. Cross-sectional studies however fail to reveal causality. Another problem is related to the failure to control for individual differences in stress susceptibility in most stress studies. Investigating psychopathologies in people that had experienced wide scale traumatic events revealed that not all people are similarly affected by these events, so that some individual were resilient to trauma. ******This new NSERC application is built on an emerging long term objective of my laboratory to reveal the functional significances and mechanisms of stress-induced hippocampal shrinkage. Using a non-invasive MRI approach to measure hippocampal volume before and after stress exposure, we have found that mice that are susceptible to chronic social defeat stress displayed stress-induced volume changes. Nonetheless, these changes were not found in mice that are resilient to chronic social defeat. Our short term objective is to use this social defeat model that allows us to separate mice that are susceptible or resilient to chronic stress to test the following hypotheses: 1) resilient mice exhibit a resistance to stress-induced hippocampal shrinkage; 2) chronic stress exerts opposing effects on the volume of the dorsal and ventral hippocampus, which are responsible for spatial and emotional memory formation, respectively, and 3) stress-induced hippocampal shrinkage is related to dendritic reorganization and microglia proliferation.******Findings from this research program could not only advance our understanding of the functional significance and mechanisms of stress-induced hippocampal shrinkage, but also allow us to develop a new research avenue for longitudinally investigating changes in mouse brain structures. This research program complements the ongoing research of my lab to investigate the impact of stress on hippocampal synaptic function. Training from this research program could equip trainees to use non-invasive imaging approaches on mice, which are powerful but newly emerging research techniques that could help them develop their career in both academia and industry.